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Uncovering the science behind 'sound body, sound mind'

Researchers from the Karolinska Institutet in Sweden get to grips with the molecular basis of the saying "sound mind, sound body." The key appears to be how muscles reduce levels of stress markers in the blood.

A new study explains how muscle activity benefits the whole body.

Studies have shown that exercising not only promotes burning fat but also benefits the mind.

Even before science understood why, carrying out physical activity was already considered useful in reducing depressive symptoms for some people.

In 2014, for the first time, a group of researchers from the Karolinska Institutet described exactly how exercise might benefit the brain.

The Swedish team showed that when muscles were put to work during exercise, they produced an enzyme that broke down kynurenine – a compound that is present at higher levels in people with depression and other mental disorders.

The enzyme produced by muscle converts kynurenine into kynurenic acid, which cannot cross the blood-brain barrier. In this way, the brain is protected from certain stress-induced changes that are thought to occur in depression.

Effectively, the muscles clear the blood of this compound, preventing its negative consequences in the brain.

Examining kynurenine in more detail

This week, the same team of scientists mentioned above release their findings from the latest study to probe this mechanism; the results are published in the journal Cell Metabolism.

In their latest study, they delve deeper into this relationship and examine how kynurenine benefits more than just the brain; its impact is wide-ranging. The project was lead by Jorge Ruas, from the Department of Physiology and Pharmacology at the Karolinska Institutet.

They demonstrate that the previously outlined relationship goes both ways, explaining that the same reduction in kynurenine that helps reduce depression also boosts fat metabolism and the anti-inflammatory response.

For the study, the team fed rats a high-fat diet that increased their blood sugar levels and made them overweight. Then, they gave the mice a daily injection of kynurenic acid, the breakdown product of kynurenine. The mice treated with kynurenic acid continued to be fed the high-fat diet.

Despite no change in caloric intake, the mice stopped putting on weight and their glucose tolerance — a marker for metabolic disorders — improved.

This mechanism may provide hope

The researchers believe that kynurenic acid works at a receptor known as GPR35, which is found on fat cells and within the immune system.

It is possible that, through kynurenic acid's activity at this receptor, white fat is turned into brown fat, which can boost metabolism and lower blood glucose levels; at the same time, its ability to interact with immune cells may reduce damaging inflammation.

"We've linked the two parts of the expression 'sound mind, sound body.' Our research adds to the understanding of why exercise training benefits the body and, in the long run, can lead to the development of new treatments for obesity or diabetes."

Jorge Ruas

This novel pathway by which exercise might impact the brain, body, and immune system has the potential to spark the design of innovative interventions. If modulating the kynurenine pathway can reduce weight gain without a change in diet, it could provide a novel target for treatments.

As obesity and diabetes continue to be a huge public health concern across America, understanding, in more detail, how they might be curbed or prevented is heartening.

However, as the authors note, these are early trials, and there is a long path ahead; as Ruas says, "Our next step is to identify the complex chain of interacting molecules that's affected by diet and training."

This will be a challenging and detailed task, but the team at the Karolinska Institutet are determined to forge ahead.

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